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Add-ons (Time-lapse, MACS, EmbryoGlue, etc.). What you need to ask about additional treatments?

Tatiana Chartomatsidou, MSc
Clinical Embryologist , Assisting Nature – Human Reproduction & Genetics

Category:
Genetics PGS / PGT-A, IVF laboratory, Male Factor

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From this video you will find out:
  • What is an IVF add-on?
  • Time-lapse imaging – is it useful, and how does it work?
  • What is MACS (Magnetic-activated cell sorting) for cell sorting?
  • What is Intracytoplasmic morphologic sperm injection (IMSI), and when is it indicated?
  • Does Physiological intracytoplasmic sperm injection (PICSI) increase pregnancy rates?
  • How EmbryoGlue can help with embryo transfer?
  • How does Assisted Hatching work, and how does it affect success rates?
  • What are IVF outcomes after PGT-A biopsy?

Add-ons (Time-lapse, MACS, EmbryoGlue, etc.). What you need to ask about additional treatments?

During this session, Tatiana Chartomatsidou, Clinical Embryologist at Assisting Nature, explained additional IVF treatment procedures, including Time-lapse, MACS, EmbryoGlue, Assisted Hatching, PICSI, IMSI and its usefulness.

Tatiana started her presentation by defining what an add-on means. It’s any technique that is a variation or done as an add-on from the routine in the IVF cycle. It means that these techniques are not essential for your treatment, and they may include the laboratory clinker or other complementary. They are usually new techniques, and they aim to improve the chances of IVF success.

Time-lapse imaging

Normally, when an embryo is cultured, specific incubators are used where the embryos are placed. At specific time points of the culture, the embryos are taken out of the incubator, so the embryologists can observe them under the microscope. This means that despite it takes only a couple of minutes, the embryo conditions are interrupted. Thanks to time-lapse technology, which has cameras inside, embryologists can monitor the embryos without taking them out. This can help to select the best embryo and select it for embryo transfer and freeze.

MACS (Magnetic-activated cell sorting)

MACS technique can help to identify the apoptotic cells in the sperm using an immunogenetic test. Normally, embryologists select the best sperm based on morphology and motility, but this does not mean it is 100% accurate. Apoptotic cells mean that they are damaged, which means this sperm is not suitable for fertilization. Thanks to this technique, it’s possible to sort out damaged sperm and choose only the ones that have a low fragmentation rate. This way, we can improve the overall quality of the sperm that is going to be used and then the embryo quality and the pregnancy rates. This technique does not have any clinical adverse effects at the obstetric and perinatal levels. It is usually used when there is a severe male factor, when there is high DNA fragmentation index, in cases of repeated miscarriages with unidentified causes, previous failed IVF cycles or poor embryo quality, which is not attributed to the eggs.

IMSI (Intracytoplasmic morphologically selected sperm injection)

It’s a method that allows the intracytoplasmatic sperm injection of morphologically selected sperm. The sperm is seen with high magnification (6000 to 6600), and it allows the embryologists to choose only the healthiest sperm with the best morphology. This method is used when spermatozoa have mitochondrial dysfunction or DNA damage. It helps to identify spermatozoa with a normal nucleus and nuclear content. IMSI can contribute to improving the success rates in patients diagnosed with oligo-asthenoteratozoospermia. According to studies, it has been shown that this particular method can lead to better fertilization rates, better embryo quality and, in consequence, better pregnancy rates. In addition, IMSI is a great technique for couples with unexplained infertility or repeated implantation failures.

IMSI is a morphological selection of spermatozoa. Special lenses are used on the microscope to select only the best sperm. Compared to ICSI, it has a much higher level of magnification as it is 6300 x, while with ICSI, it is at 400x magnification. It allows to detection potential defects in the head or middle piece of spermatozoa. Thanks to this method, it’s possible to select the best sperm and decrease the chances of poor quality sperm, which can lead to implantation failure or higher miscarriage risk and in the end, we can improve the pregnancy rates.

IMSI is usually suggested in cases of teratozoospermia or with a severe High DNA fragmentation index, previous fertilisation failure after ICSI, in couples with a history of poor quality embryos or implantation failures and cases of long-term unexplained infertility.

PICSI (Physiological intracytoplasmic sperm injection)

PICSI is a variant of traditional ICSI. As mentioned before, the embryologist selects the sperm based on its motility and morphology, so this is something that can be subjective. PICSI helps with making the process a bit less objective because special dishes are used which have some drops of synthetic material, very similar to hyaluronic acid.

This acid is usually found at the top of the oocytes. What the embryologists try to do is use a synthetic material that combines only the material’s parameters with it. It can be retained and remain attached to these drops, ruling out any other immature or low-quality sperm. The embryologists can use only the best ones – only the highest quality sperm. This technique aims to make the whole procedure less subjective, and more objective and simple. It can help increase pregnancy rates and decrease abortion rates. It is usually suggested for couples with high DNA fragmentation rates or unexplained fertility. It is also recommended in cases of repeated miscarriages, previous failed IVF cycles or cases with a history of unsuccessful IVF attempts. However, it is not suitable for cases of very low sperm motility or low sperm count.

EmbryoGlue

Embryoglue contains hyaluronan, which acts as a bridge between the embryo and the womb. This solution has an optimal composition with a high concentration of hyaluronan and human albumin, supporting the embryo and facilitating implantation in the womb. One of its characteristics is its similarity to the uterine environment, minimizing embryo drifting and aiding the implantation procedure. Studies have shown that using EmbryoGlue can lead to higher delivery rates and an increased chance of multiple births.

Assisted hatching

Assisted hatching is performed in the lab to help the embryo hatch from the zona pellucida. The zona pellucida is a protective layer surrounding the embryo from the early stages of development until the blastocyst stage. Normally, the blastocyst will hatch from the zona to implant in the uterus. When we perform assisted hatching, we create a small hole in the zona, allowing the embryo to easily escape. This technique has shown an increase in clinical pregnancy rates, although there isn’t a significant difference in delivery rates. It is usually performed in special cases to facilitate the results. Typically, assisted hatching is performed in cases of advanced maternal age and when the embryos have a hardened zona pellucida, making natural hatching more difficult. It is also chosen in cases of previous IVF failures or when the quality of the zona pellucida requires it.

Pre-implantation genetic testing (PGT)

Pre-implantation genetic testing (PGT) is performed to genetically assess embryos, determining which ones are suitable for transfer – the ones that are normal and can lead to a healthy pregnancy and live birth. The testing involves performing a biopsy of the embryo on the fifth day of culture when the embryo reaches the blastocyst stage. A small number of cells are removed for genetic testing, and the embryo is then frozen until the test results are available. It’s important to clarify that the cells that give rise to the embryo itself are not touched during the biopsy. Only trophectoderm cells, which will develop into the placenta, are used for testing. PGT is performed to avoid transferring abnormal embryos, as they can lead to failed implantation, miscarriages, or pregnancies with genetic conditions. By selecting normal embryos, delivery rates can be improved. PGT is usually suggested in cases of advanced maternal age, recurrent IVF failures, couples with a history of recurrent miscarriages, and cases where one or both potential parents have abnormal karyotypes.

There are many techniques available, some of which have been in routine practice for years. However, new techniques are constantly being developed, and we can expect to see more shortly. All of these techniques aim to improve the outcomes of fertility treatments. It’s important to offer these techniques responsibly, taking into account the couple’s history and each case. In IVF, every case is unique, and the focus is always on the couple. Treatment options should be determined based on the suggestions of the physicians to provide the best solution and achieve a successful and healthy live birth, which is the ultimate goal.

- Questions and Answers

My partner has severe teratozoospermia, with only 1% normal sperm. Which add-on technique would be beneficial in this case?

In the case of severe teratozoospermia, the recommended add-on technique would be IMSI, which aims to choose the best morphologically normal sperm for fertilization.

According to HFEA, there is not enough evidence to support the usefulness of IMSI. Do you perform IMSI at your clinic?

HFEA has a traffic light system that assesses various add-ons, including IMSI. While IMSI can help with sperm selection, there is not enough evidence to support its usefulness in terms of higher success rates. However, the main aim is to always have higher fertilisation and blastulation rate.

What are your thoughts on preferring ICSI versus IMSI as add-ons? What about PICSI dish since it’s only an outer sperm member binder?

ICSI can be considered as an add-on technique in certain cases where conventional IVF is not suitable. IMSI is a variation of ICSI and can help maximize the selection of the best sperm. PICSI dish is a method to eliminate immature sperm and improve selection. Both techniques have their benefits and can be used based on individual cases.

Why does implantation fail and what tests should be done? My progesterone was only 11.2 ng on transfer day and 20 ng on official testing day. Could low progesterone levels be a cause of implantation failure?

Implantation failure is a complex issue and can be caused by various factors, including embryo quality, uterine factors, or other parameters. Progesterone levels alone may not be the sole cause of implantation failure. It is important to assess the medical history of the patient and consider multiple factors to determine the cause and appropriate course of action.

My partner and I have been recommended artificial oocyte activation due to failed fertilization. What are your thoughts on this add-on procedure?

Artificial oocyte activation can be used in cases of failed fertilization. However, the necessity of this add-on procedure depends on the specific details of the previous treatment. It is important to consider both egg and sperm quality when addressing fertilization failure.

Can you provide information about microfluidic chip sperm sorting and its use in sperm preparation?

Microfluidic chip sperm sorting is an alternative method for sperm preparation that minimizes stress on sperm and can be helpful in cases with high levels of abnormal sperm. This technique allows for the selection of the best sperm samples and can be used in IUI, IVF, or ICSI procedures.

What is your opinion on time-lapse imaging for embryo development?

Time-lapse imaging provides additional information about embryo development and allows continuous observation throughout the culture period. While it may not necessarily improve success rates, it helps embryologists monitor embryos more closely and identify potential issues. It is particularly useful in cases of previous failures or when performing PGT.

Is Zymot necessary if the sperm parameters are fair?

Zymot, as a microfluidic chip technique, can help improve the quality of the sperm sample by minimizing stress caused by traditional preparation methods. It is beneficial, especially in cases of abnormal sperm morphology, but can also be used for other couples depending on their specific needs.

What is the probability that an embryo does not survive the biopsy during PGT?

The biopsy during PGT is an invasive procedure and carries a small risk of embryo damage. However, in experienced hands, the risk is minimized. The majority of cases do not experience embryo damage due to biopsy. PGT allows for the selection of normal embryos, but there is always a possibility of embryo loss or lower implantation rates

Would you ever add calcium to non-fertilized embryos to compare results with normal ART?

Adding calcium to non-fertilized embryos is not a routine procedure. It is performed through the media used for oocyte activation, typically in cases of previous fertilization failures. The decision to perform this procedure is based on the medical history of the couple. It is performed on the entire cohort, not just the non-fertilized ones, on the day of fertilization. The purpose is to enhance fertilization rates.

Which add-on would you recommend for advanced maternal age (43) and a partner with teratozoospermia?

For couples with advanced maternal age, we usually recommend performing preimplantation genetic testing for aneuploidy (PGT-A) to test the embryos for chromosomal abnormalities. Advanced maternal age is associated with higher rates of aneuploid embryos. Additionally, considering the partner’s teratozoospermia, the selection of the best sperm is crucial. Techniques such as IMSI, PICSI, or IMS, perhaps Zymot can be considered for sperm selection.

What is the main technique for sperm preparation in your lab, and do you provide all the mentioned add-ons?

The main technique for sperm preparation in our lab is swim-up or density gradient centrifugation. However, we also perform other techniques based on specific characteristics, such as microfluidics. As for the mentioned add-ons, we provide them, but the selection of add-ons depends on individual cases. Not all add-ons are suitable for every couple, as each case requires personalized treatment.

Are 100% out of the cells in a euploid blastocyst normal cells, or is there a small amount of abnormal cells that may die or not survive over time?

Yes, a blastocyst is typically composed of approximately 120 cells. When we perform PGT, the term euploid refers to a blastocyst with a normal chromosomal composition, while aneuploid refers to abnormal chromosomal conditions. During the biopsy procedure, we isolate a small number of cells that will develop into the placenta, not the embryo itself. These cells, usually around five to ten, are tested by geneticists, who provide information on whether the blastocyst is normal or abnormal. It would be best to consult a geneticist for a more detailed explanation, as this process involves cooperation between the embryology and genetic labs.

Does saving cord blood at birth when using a surrogate, where the sperm is from the father and an egg donor is used, help cure the baby from any diseases in the future?

Saving cord blood for potential future use in curing diseases has been a controversial topic. However, this is not a procedure performed by embryologists in the embryology lab. From what I have read in the literature, saving cord blood may have limited or no significant impact on curing diseases. As it is not within my field of expertise, I recommend consulting other specialists who can provide more accurate information.
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Authors
Tatiana Chartomatsidou, MSc

Tatiana Chartomatsidou, MSc

Tatiana Chartomatsidou is a Clinical Embryologist and became a member of Assisting Nature Team in 2017, as our younger trainee embryologist. She graduated with a Bachelor of Science degree in Biology from the Aristotle University of Thessaloniki in 2013 focusing in the field of Molecular Biology, Genetics and Biotechnology. Master's degree in Aristotle University of Thessaloniki, attending the Postgraduate Study Program “Applied Genetics and Biotechnology”, where she was involved in the challenging field of Molecular Biology and Cytogenetic. In her thesis, she performed mitochondrial DNA and chromosome analysis, using molecular and cytogenetic techniques, along with the use of bioinformatic tools.
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Caroline Kulczycka

Caroline Kulczycka

Caroline Kulczycka is managing MyIVFAnswers.com and has been hosting IVFWEBINARS dedicated to patients struggling with infertility since 2020. She's highly motivated and believes that educating patients so that they can make informed decisions is essential in their IVF journey. In the past, she has been working as an International Patient Coordinator, where she was helping and directing patients on their right path. She also worked in the tourism industry, and dealt with international customers on a daily basis, including working abroad. In her free time, you’ll find her travelling, biking, learning new things, or spending time outdoors.